Randomized Trial of TAVI vs. SAVR in Patients With Severe Aortic Valve Stenosis at Low to Intermediate Risk of Mortality

Aortic Valve Stenosis Clinical Trial

— DEDICATE  

Official title:

Randomized, Multi-Center, Event-Driven Trial of TAVI Versus SAVR in Patients With Symptomatic Severe Aortic Valve Stenosis and Intermediate Risk of Mortality, as Assessed by STS-Score - DEDICATE

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03112980
• Other study ID #: DEDICATE
• Secondary ID: DEDICATE - DZHK
• Status: Active, not recruiting
• Phase: N/A
• Start date: May 10, 2017
• Est. completion date: January 2028

Study information

• Verified date: April 2024
• Source: Universitätsklinikum Hamburg-Eppendorf
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Randomized controlled, multi-center trial randomizing patients with symptomatic severe aortic stenosis at low to intermediate operative risk of mortality in a 1:1 fashion to transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) to test, whether TAVI is non-inferior to SAVR, as measured by all-cause mortality or stroke after 1 and 5 years.

Description:

A paradigm-shift towards performing TAVI in intermediate- and low-risk patients has already begun, as procedural results of TAVI have improved significantly within the past years. Nevertheless, a prospective and independent comparison of surgical (SAVR) and interventional (TAVI) valve therapy in patients considered at low to intermediate risk that covers an "all-comers" patient population and multiple devices has not yet been performed.

The DEDICATE-trial is designed as a prospectively randomized (1:1), multi-center, comparator-controlled interventional trial to investigate whether transcatheter aortic valve implantation (TAVI) is non-inferior - as measured by all-cause mortality or stroke after 1 and 5 years - compared to surgical aortic valve replacement (SAVR) in the treatment of patients with symptomatic severe aortic stenosis at low to intermediate operative risk of mortality, as assessed by the local Heart Team.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1414
• Est. completion date: January 2028
• Est. primary completion date: January 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years to 85 Years

Eligibility

Inclusion Criteria:

1. Heart team consensus that TAVI and SAVR are both medically justified and advisable based on:

1. Degenerative aortic valve stenosis with echocardiographically derived criteria:

• Mean gradient >40 mmHg or

• Jet velocity greater than 4.0 m/s or

• Aortic valve area (AVA) of < 1.0 cm2 (indexed effective orifice area < 0.6cm2/m2).

2. Patient is symptomatic from his/her aortic valve stenosis

• New York Heart Association Functional Class = II or

• Angina pectoris or

• Syncope.

3. Patient is classified as low to intermediate operative risk as assessed by the local heart team according to the variables outlined in the 2017 ESC/EACTS Guidelines for the Management of valvular heart disease, taking into account cardiac and extracardiac Patient characteristics and established risk scores (e.g. STS-PROM, EuroSCORE).

4. A transfemoral or alternative (e.g. transapical, transaortic, transaxillary) access for TAVI seems feasible. Centers should follow a "transfemoral first" strategy for the primary route of access; however, other routes of access are also allowed, as decided by local heart team consensus.

2. Patient has provided written informed consent to participate in the trial.

3. Ability of the patient to understand the patient information and to personally sign and date the informed consent to participate in the study, before performing any study related procedures.

4. The patient agrees to undergo SAVR, if randomized to control treatment.

5. The patient and the treating physician agree that the patient will return for all required post-procedure follow-up visits.

6. Patients aged 65 to 85 years.

7. Male patients or females who are postmenopausal defined as no menses for 12 months without an alternative medical cause.

Exclusion Criteria:

1. Aortic valve is a congenital unicuspid or congenital bicuspid valve, or is non-calcified

2. Untreated clinically significant coronary artery disease considered a contraindication to an isolated aortic valve procedure (TAVI or SAVR) according to heart team consensus

3. Previous cardiac surgery

4. Any percutaneous coronary intervention performed within 1 month prior to the study procedure

5. Untreated severe mitral or tricuspid regurgitation

6. Untreated severe mitral stenosis

7. Hemodynamic instability requiring inotropic support or mechanical circulatory support

8. Ischemic stroke or intracranial bleeding within 1 month

9. Severe ventricular dysfunction with left ventricular ejection fraction < 20% as measured by resting echocardiogram

10. Hypertrophic obstructive cardiomyopathy or severe basal septal hypertrophy with outflow gradient

11. Echocardiographic evidence of an intracardiac mass, thrombus, vegetation or endocarditis

12. Any other condition considered a contraindication for an isolated aortic valve procedure

13. Symptomatic carotid or vertebral artery disease

14. Expected life expectancy < 12 months due to associated non-cardiac comorbidities

15. Currently participating in another investigational drug or device trial

Related Conditions & MeSH terms

• Aortic Valve Stenosis
• Constriction, Pathologic

Intervention

Device:
• Transcatheter aortic valve implantation
(TAVI)

Procedure:
• Surgical aortic valve replacement
(SAVR)

Locations

Country	Name	City	State
Germany	Uniklinik Rheinisch-Westfälische Technische Hochschule Aachen	Aachen
Germany	Universitäts-Herzzentrum Freiburg-Bad Krozingen	Bad Krozingen
Germany	Kerckhoff-Klinik Bad Nauheim	Bad Nauheim
Germany	Herz- und Gefässklinik Bad Neustadt/Saale	Bad Neustadt an der Saale
Germany	Herz- und Diabeteszentrum NRW Bad Oeynhausen	Bad Oeynhausen
Germany	Charité Universitätsmedizin Berlin (Campus Benjamin-Franklin)	Berlin
Germany	Charité Universitätsmedizin Berlin (Campus Mitte)	Berlin
Germany	Charité Universitätsmedizin Berlin (Campus Virchow)	Berlin
Germany	Deutsches Herzzentrum Berlin	Berlin
Germany	Vivantes Friedrichshain	Berlin
Germany	Vivantes Humboldt Kliniken	Berlin
Germany	Vivantes Klinikum am Urban	Berlin
Germany	Vivantes Neukölln	Berlin
Germany	Immanuel Klinikum Bernau	Bernau
Germany	Kliniken der Ruhr-Universität Bochum	Bochum
Germany	Medizinische Hochschule Brandenburg Theodor Fontane	Brandenburg an der Havel
Germany	Herzzentrum Dresden an der Technischen Universität Dresden	Dresden
Germany	Universitätsklinikum Düsseldorf	Düsseldorf
Germany	Universitätsklinikum Erlangen	Erlangen
Germany	Universitätsklinikum Essen, Klinikum für Kardiologie und Angiologie am Westdeutschen Herz- und Gefäßzentrum	Essen
Germany	Universitätsklinikum Frankfurt	Frankfurt
Germany	Universitäts-Herzzentrum Freiburg-Bad Krozingen	Freiburg
Germany	Universitätsklinikum Giessen und Marburg	Giessen
Germany	Universitätsklinikum Göttingen	Göttingen
Germany	Universitätsmedizin Greifswald / Klinikum Karlsburg	Greifswald / Karlsburg
Germany	Universitätsklinikum Halle (Saale)	Halle (Saale)
Germany	Universitäres Herz- und Gefäßzentrum Hamburg (UHZ)	Hamburg
Germany	Medizinische Hochschule Hannover	Hannover
Germany	Universitätsklinikum Heidelberg	Heidelberg
Germany	Universitätsklinikum Jena	Jena
Germany	Universitätsklinikum Schleswig-Holstein	Kiel
Germany	Bundeswehrzentralkrankenhaus Koblenz	Koblenz
Germany	Herzzentrum der Uniklinik Köln	Köln
Germany	Deutsches Herzzentrum Leipzig	Leipzig
Germany	Universitäres Herzzentrum Lübeck	Lübeck
Germany	Otto-von Guericke-Universität Magdeburg	Magdeburg
Germany	Universitätsmedizin Mainz	Mainz
Germany	Deutsches Herzzentrum München	München
Germany	LMU Klinikum der Universität München	München
Germany	Universitätsklinikum Münster	Münster
Germany	Universitätsklinikum Regensburg	Regensburg
Germany	Robert Bosch Krankenhaus	Stuttgart
Germany	Universitätsklinikum Ulm	Ulm

Sponsors (3)

Lead Sponsor	Collaborator
Universitätsklinikum Hamburg-Eppendorf	Deutsche Herzstiftung e.V., Deutsches Zentrum für Herz-Kreislauf-Forschung (DZHK)

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Blankenberg S, Seiffert M, Vonthein R, Baumgartner H, Bleiziffer S, Borger MA, Choi YH, Clemmensen P, Cremer J, Czerny M, Diercks N, Eitel I, Ensminger S, Frank D, Frey N, Hagendorff A, Hagl C, Hamm C, Kappert U, Karck M, Kim WK, Konig IR, Krane M, Landmesser U, Linke A, Maier LS, Massberg S, Neumann FJ, Reichenspurner H, Rudolph TK, Schmid C, Thiele H, Twerenbold R, Walther T, Westermann D, Xhepa E, Ziegler A, Falk V; DEDICATE-DZHK6 Trial Investigators. Transcatheter or Surgical Treatment of Aortic-Valve Stenosis. N Engl J Med. 2024 Apr 8. doi: 10.1056/NEJMoa2400685. Online ahead of print. — View Citation

Seiffert M, Vonthein R, Baumgartner H, Borger MA, Choi YH, Falk V, Frey N, Hagendorff A, Hagl C, Hamm C, Konig IR, Landmesser U, Massberg S, Reichenspurner H, Thiele H, Twerenbold R, Vens M, Walther T, Ziegler A, Cremer J, Blankenberg S. Transcatheter aortic valve implantation versus surgical aortic valve replacement in patients at low to intermediate surgical risk: rationale and design of the randomised DEDICATE Trial. EuroIntervention. 2023 Oct 23;19(8):652-658. doi: 10.4244/EIJ-D-23-00232. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Freedom from stroke or death	(Efficacy endpoint)	within 5 years after randomization
Primary	Freedom from stroke or death	(Safety endpoint)	within 1 year after randomization
Secondary	Freedom from stroke or death	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Overall survival	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from cardiovascular mortality	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from the composite of all-cause mortality and stroke	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from myocardial infarction	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from stroke	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from major or life-threatening / disabling bleeding	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from acute kidney injury	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from vascular access site and access-related complications	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from conduction disturbances and arrhythmias, need for permanent pacemaker implantation	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from residual aortic regurgitation = moderate	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Composite device success	Number of participants with freedom from procedural mortality and correct positioning of a single transcatheter heart valve (THV) in the proper position with intended performance (no prosthesis- patient mismatch and mean aortic valve gradient <20 mmHg or peak velocity <3 m/s, AND no moderate or severe prosthetic valve regurgitation)	Five years after last patient in
Secondary	Composite early safety	Number of participants dying and/or number of participants with stroke (disabling and non-disabling), and/or life-threatening bleeding and/or acute kidney injury stages 2/3 and/or coronary artery obstruction requiring Intervention and/or major vascular complication and/or valve-related dysfunction requiring repeat procedure.	within first 30 days after procedure
Secondary	Composite clinical efficacy	Number or participants dying and/or number of participants with stroke (disabling and non-disabling) and/or rehospitalisation for worsening heart failure or valve-related symptoms and/or New York Heart Association functional class (NYHA) III or IV and/or valve-related dysfunction (mean aortic valve gradient >20 mmHg, effective orifice area (EOA) <0.9-1.1 cm2 and/or Doppler Velocity Index (DVI) <0. 35 m/s, AND/OR moderate or severe prosthetic valve regurgitation)	within first 30 days after procedure
Secondary	Freedom from prosthetic valve dysfunction	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from prosthetic aortic valve endocarditis	will be assessed at every study visit and compared between TAVI and SAVR groups	Five years after last patient in
Secondary	Freedom from the composite time-related valve safety	Number of participants with structural valve deterioration (including repeat procedures, prosthetic valve endocarditis and/or thrombosis) and/or number of participants with thromboembolic events (stroke) and/or Valve Academic Research Consortium (VARC-2) bleeding (unless clearly unrelated to valve therapy).	Five years after last patient in
Secondary	Quality of life measures	Number of participants with reduced quality of life measures after valve replacement as compared to baseline levels prior to valve-replacement, assessed using EuroQol five dimensions (EQ-5D) questionnaire and/or Barthel Index and/or center for epidemiologic studies depression (CES-D) Scale.	Five years after last patient in
Secondary	Health economic analysis	Incremental cost-effectiveness of TAVI compared to surgical valve replacement, by using quality adjusted life years (QALYs).	Five years after last patient in
Secondary	Number of (re) hospitalisations	Number rehospitalisations of all participants. Length of stay in hospital	Five years after last patient in